A majority of social skills research in autism spectrum disorder (ASD) and interventions target school age males and no published studies target adolescent females with ASD or related disabilities. Females with ASD are at risk for internalizing symptoms, and experience greater challenges in socialization and communication as social demands become increasingly complex in adolescence. This paper provides a thorough description of a social skills and self-care program designed to address the specific needs of adolescent females with ASD. The approach is peer mediated and occurs within natural or community settings to facilitate generalization. Findings from program evaluation data collected across 4 years illustrate significant improvements in perceived social competence, self-perception, and quality of life and suggests the approach is feasible and social valid.